The cyclic somatotropin-release inhibiting factor (SRIF), known as somatostatin, has been shown [Brazeau et al., Science, 179, 77 (1973)] to have the following structure: ##STR1## all amino acids being of the "natural" or L configuration.
Several methods for synthesizing somatostatin have been reported in the literature including the solid phase method of Rivier, J. Am. Chem. Soc., 96, 2986 (1974), and the solution methods of Sarantakis et al., Biochemical Biophysical Research Communications, 54, 234 (1973), and Immer et al., Helv. Chim. Acta, 57, 730 (1974); and there is much on-going peptide research whose goal is to enhance somatostatin's pharmacological activity by synthetically modifying its structure.
The present invention provides novel analogs of somatostatin wherein the Ala.sup.1 -Gly.sup.2 residue is either present or may be replaced with H, L-Ala-Gly, L-Ala-D-Ala, Gly-Gly-Gly, or Gly-Gly; the L-Trp.sup.8 residue is either present or may be replaced with D-Trp.sup.8 ; the L-Lys.sup.4 -L-Asn.sup.5 residue is replaced with L-Arg.sup.4 -L-His.sup.5 ; and the L-Cys.sup.14 residue is either present or replaced with D-Cys.sup.14.
Replacement of the L-Trp residue in somatostatin by D-Trp.sup.8 is discussed by J. Rivier et al., Biochem. Biophys. Res. Commun., 65, 746 (1975).
Somatostatin analogs wherein the L-Lys.sup.4 -L-Asn.sup.5 residues are replaced with various other amino acid residues are disclosed in Belgian Pat. No. 839,405.
Analogs of somatostatin in which the first two amino acids, Ala-Gly, are not present have been reported by J. Rivier et al., J. Med. Chem., 18, 123 (1975).